tbuckley/cabot-search huggingface dataset:
Abstract 11588: Multicenter Development and Validation of a Machine Learning Model to Predict Myocardial Recovery During LVAD Support: The UCAR Score
Authors: Christos P Kyriakopoulos, Iosif Taleb, Omar Wever-Pinzon, Craig H Selzman, Abdallah Kfoury, Michael J Bonios, James Wever-Pinzon, Michael Y Yin, Eleni Tseliou, Josef Stehlik, Rami Alharethi, William Caine, James C Fang, Antigone G Koliopoulou, Konstantinos Sideris, Marisca Nelson, Ashley Elmer, Elizabeth Dranow, Ramesh Singh, Mitchell Psotka, Emma J Birks, Mark S Slaughter, Steven Koenig, Andreas Kyvernitakis, Karlee Hoffman, Maya Guglin, John Kotter, Kenneth S Campbell, Scott C Silvestry, Andrija Vidic, Nirav Raval, Jennifer Cowger, Manreet Kanwar, Palak Shah, Stavros G Drakos
Journal: Circulation (2022)

Introduction: Although significant cardiac reverse remodeling is a prerequisite for a left ventricular (LV) assist device (LVAD) patient to be considered for device weaning, multiple factors including patient goals, physician comfort, and center experience, weigh in on this complex decision. Existing predictive models defining recovery as device removal may under detect patients that could benefit from a targeted bridge to recovery strategy. We sought to derive and validate a predictive tool to identify patients prone to reverse remodel, independent of the complex decision of device explant. Methods: Heart failure patients (N=782) requiring LVAD were enrolled at the Utah Transplant Affiliated Hospitals (n=537) and 5 US programs (n=245). Baseline characteristics were recorded. The primary outcome was ‘responder’ incidence, defined as follow-up LV ejection fraction (LVEF) ≥40% and LV end-diastolic diameter (LVEDD) ≤6 cm within one year on LVAD support. Bootstrap imputation and lasso variable selection techniques were used to derive a predictive model which was then validated. A predictive calculator was developed and patients were classified into groups with varying potential for reverse remodeling. Results: Patients were predominantly white (84%), males (82%), aged 56±1 years. Overall, 14.8% patients were identified as responders. A subset of 10 pre-operative variables associated with reverse remodeling were included in the multivariate model achieving an optimism-corrected C-statistic of 0.75 (95% CI: 0.73-0.84) (Figure) . Conclusions: The UCAR calculator is a machine learning-based multicenter and validated risk tool, implementing routine pre-operative clinical data, effectively stratifying patients into groups with varying potential for reverse remodeling. This tool can be useful in selecting patients to implement diagnostic and therapeutic protocols to promote reverse remodeling and myocardial recovery.
Abstract 11738: Epicardial Connections as an Etiology in Recalcitrant Tachyarrhythmias After Left Atrial Ablations in Patients With Persistent Atrial Fibrillation
Authors: Yaser Carcora, Emily Zhi, Smitha Murthy, Stephanie Li, Selcuk Adabag, Venkatakrishna N Tholakanahalli
Journal: Circulation (2022)

Introduction: Left atrial radio frequency ablation(RFA) for persistent atrial fibrillation(AF) and left atrial tachycardias(LAT) are often challenging due to the presence of epicardial connections(EC). Hypothesis: Mapping and subsequent ablation of epicardial connections using high density(HD) mapping and activation patterns leads to successful termination of persistent AF and LAT. Methods: We studied 40 patients who were found to have epicardial connections as determined by HD mapping, missing isochrones and activation patterns. All patients underwent antral ablation for pulmonary vein isolation (PVI). LAT were remapped using Advisor HD Grid catheter. Results: At baseline, the mean age and BMI was 74±6.4 and 33.5±5.8 respectively. Out of 40 patients with EC, 21 were associated with the Vein of Marshall (Figure 1), 4 were associated with Septo-pulmonary bundles(figure 2), 6 were associated with the Bachman Bundle(Figure 3) and 9 were associated with Septo-atrial bundles. Acutely, endocardial ablation opposite to the epicardial connection sites achieved success with PVI, Posterior Wall Isolation(PWI) and termination of LAT. Conclusions: EC significantly contributes to the failure of PVI, PWI and the reorganization of LAT. Rigorous mapping of the connecting bundles using HD mapping helps target the ablation sites for successful outcomes.
Abstract 12480: Changes in Tmao Levels Following Bariatric Surgery Vary by Procedure Type
Authors: Beth H Sherry, Ruina Zhang, Michela Garabedian, Jeffrey S Berger, Sean P Heffron
Journal: Circulation (2022)

Introduction: Trimethylamine-N-oxide (TMAO), a metabolite generated by the gut microbiota from dietary phosphatidylcholine and carnitine, is linked to atherosclerosis and thrombosis. Although bariatric surgery improves CV outcomes, several studies in both animals and humans have shown increased TMAO levels after bariatric surgery. We tested the impact of the two most common bariatric procedures on plasma TMAO. Methods: This study included 93 severely obese non-diabetic individuals who did not take diabetes or lipid-lowering medications and underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Plasma TMAO was measured before and ≥ six months after bariatric surgery. Results: Mean age of the subjects was 31.4 ± 7.2 years and 90% were female. At baseline, average weight and BMI were 117.1 ± 24.4 kg and 43.4 ± 8.0 kg/m 2 respectively. Average baseline plasma TMAO level was 2.2 ± 1.4 μM. 29 patients underwent RYGB and 64 patients underwent SG. There were no significant differences in baseline weight, BMI, or TMAO between procedures. RYGB patients lost significantly more weight than SG patients (37.5 ± 8.6 kg for RYGB vs 32.8 ± 9.0 kg for SG, p = 0.03). TMAO levels did not change following SG, whereas they increased after RYGB ( Figure ). Changes in TMAO were not associated with changes in other clinical measures, for example, body weight and BMI ( Figure ) for either RYGB or SG patients. Conclusions: We found contrasting responses in circulating TMAO following bariatric surgical procedures employing dissimilar anatomical alterations. Given TMAO-associated CVD risk, these differences may lead to contrasting CV outcomes in the future. Additional research to understand changes in TMAO and the microbiota after bariatric surgery, and their clinical relevance, are warranted.
Abstract 11899: Biomarker Profile Associated With Provider Assessed Frailty in Advanced Heart Failure Patients Undergoing Lvad: An Intermacs Analysis
Authors: Keshvi Chauhan, Adam Kuchnia, Timothy Hess, Heather Lorden, Ashley Macy, Farhan Raza, Ravi Dhingra
Journal: Circulation (2022)

Introduction: Frailty is a state of increased vulnerability and decline in multi-organ physiologic reserve. Among patients considered for left ventricular assist device (LVAD), frailty is associated with increased morbidity and mortality. However, a biomarker profile that is associated with the presence of frailty and reflects multiorgan dysfunction is unknown. Methods: We selected all patients from Interagency Registry for Mechanical Assisted Circulatory Support (INTERMACS) national database who underwent an LVAD between years 2006-2017 and had available data on provider-assessed frailty (n=21,977; 4,659 females). Then, using several pre-implant variables (n=32) such as vitals, right heart catheterization hemodynamics, echocardiographic and serum biomarkers we created a stepwise multivariable logistic regression model that allowed every variable to enter or leave the model at a significance of 0.05 to examine the odds of provider-assessed frailty prior to LVAD. Results Frailty was present in 968 patients (238 females; mean age 63.1yrs). Frail patients were more likely to be older, had higher levels of blood urea nitrogen (BUN), alanine transaminase, total bilirubin, lactate dehydrogenase, B-type natriuretic peptide (BNP), N-terminal proBNP, international normalized ratio (INR) and white blood cell counts but lower albumin, prealbumin, hemoglobin and platelet counts (p &lt;0.05 for all comparisons). In stepwise logistic regression model, advancing age, higher bilirubin, BUN, INR and a lower albumin, hemoglobin, creatinine and platelets levels were the remaining variables associated with higher odds of frailty (see table). Conclusion In our study, 7 commonly obtained serum biomarkers and age were associated with presence of frailty. Future studies will examine if treatment that ensures modifying these biomarkers can reduce the risk of post-LVAD morbidity and mortality. Table
Abstract 12421: Assessment of Flow Measurements Using a Noninvasive Photoplethysmography-Based Device Compared to Invasive Pulmonary Artery Catheter
Authors: Dean Nachman, Eldad Rahamim, Mahsati Ibrahimli, Asen G Asenov, Nir Goldstein, Yotam Kolben, Segev Huly, Arik Ben Ishay, Meir Fons, Roei Merin, Arik Eisenkraft, Offer Amir, Rabea Asleh
Journal: Circulation (2022)

Introduction: Invasive monitoring is considered the gold standard of hemodynamic monitoring, yet it is associated with inherent risks. We compared advanced hemodynamic measurements taken using a noninvasive wearable photoplethysmography-based (PPG) monitor and an invasive Swan-Ganz catheter (SGC). Methods: Patients with a prior diagnosis of heart failure undergoing right heart catheterization as part of their clinical assessment were recruited. The noninvasive PPG monitor was applied and readings of cardiac output (CO) and stroke volume (SV) commenced in parallel to the invasive hemodynamic study. Bland-Altman plots and Pearson’s correlations were used to assess the accuracy and degree of agreement between techniques. Results: 90 patients (19-89yo, 53 males) were recruited and included in the final analysis. The mean values of the CO measured using the indirect Fick method, the PPG device, and the thermodilution (TD) method was 5.0±1.4 L/min, 4.9±1.3 L/min, and 4.9±1.6 L/min, respectively. Bland-Altman analysis showed that the PPG had a bias of 0.1 L/m (1.7 - -1.5 L/m 95% LOA) and the TD had a bias of 0.2 L/m (2.2 - -1.8 L/m 95% LOA). The mean SV with the indirect Fick method, the PPG device, and the TD method were 63.6±20.2 mL/beat, 62.0±17.0 mL/beat, and 61.3±20.8 mL/beat, respectively. Bland-Altman analysis showed that the PPG device had a bias of 1.6 mL/beat (23.2 - -20.0 mL/beat 95% LOA) and the TD had a bias of 2.3 mL/beat (28.3 - -23.7 mL/beat 95% LOA). Correlations between the indirect Fick method and the PPG device, and between the indirect Fick method and the TD method were 82.5% and 77.7% for CO, and 83.7% and 79.6% for SV, respectively. Conclusions: The PPG device provides CO and SV measurements that highly correlate with the gold standard invasive indirect Fick method, similarly to the invasive thermodilution method.
Abstract 11760: Depression Paradox for In-Hospital Cardiovascular Outcomes in Obstructive Sleep Apnea - A National Population-Level Analysis
Authors: Rupak Desai, Sai Shanmukha Sreeram Pannala, Pratiksha Shankarlal Nathani, Avinaash Raja Sager, Warda Shahnawaz, Dharshana Prem Anand, April Kristine Miguel, Sai Prasanna Lekkala, Aleen Rahman, Sashwath Srikanth
Journal: Circulation (2022)

Background: ​​Depression is a frequently encountered comorbidity in patients with Obstructive Sleep Apnea (OSA), with a higher prevalence than the general population. However, there is limited data on the impact of psychiatric comorbidities on the outcomes of OSA. Methods: We identified OSA hospitalizations using the National Inpatient Sample (2018) and relevant ICD-10 codes. After propensity score matching, demographics and comorbidities were compared between the two groups of OSA with (OSA-D+) vs without depression (OSA-D-). The odds of in-hospital outcomes between them were analysed using multivariable regression analyses. Results: Of the 2169730 OSA hospitalizations, 20.1% had comorbid depression. Matched cohorts included 846150 admissions in both groups - OSA-D+ and OSA-D-.The OSA-D+ cohort often consisted of younger (median age, 64 vs 65); females (55.5% vs 55.2%) with both cohorts predominantly including white, Medicare enrollees. The OSA-D+ cohort had significantly higher rates (all p&lt;0.001) of comorbidities such as Hypertension (68.6% vs 64.6%); Diabetes (48.4% vs 47.4%); Hyperlipidemia (59.2% vs 53.5%); Congestive Heart Failure (21.7% vs 20.6%); Peripheral Vascular Disease (6.7% vs 6.3%); Anemia (22.4% vs 19.7%); Smoking (44.6% vs 41.8%); Substance abuse, prior MI,TIA/Stroke and Venous Thromboembolism compared to the OSA-D- group. Paradoxically, there was decreased all-cause mortality (OR:0.79, 95%CI 0.73-0.86), major adverse cardiac and cerebrovascular events (OR:0.83, 95%CI 0.80-0.87), acute MI (OR:0.80, 95%CI 0.76-0.85), dysrhythmia/AF (OR:0.81, 95%CI 0.79-0.83) and cardiac arrest including VF (OR:0.65, 95%CI 0.73-0.82) in the OSA-D+ cohort cohort during hospitalization (p&lt;0.001). Conclusion: Despite having more comorbidities, OSA patients with depression were found to have better in-hospital outcomes. Further studies are required for a conclusive reason for this paradoxical effect of co-morbid depression.
Abstract 11785: Phenotype Features of Coronary Atheroma in Association With an Elevated Activity of Pericoronary Adipose Tissue (Insights From Computed Coronary Angiography and Near-Infrared Spectroscopy Analysis)
Authors: Satoshi Kitahara, Yu Kataoka, Hiroyuki Miura, Tatsuya Nishii, KOTA MURAI, Takamasa Iwai, Kenichiro Sawada, Hideo Matama, Satoshi Honda, Masashi Fujino, Shuichi Yoneda, Kensuke Takagi, Fumiyuki Otsuka, Yasuhide Asaumi, Yusuke Fujino, Kenichi Tsujita, Teruo Noguchi
Journal: Circulation (2022)

Introduction: Inflammation has been considered to promote atheroma instability. Coronary computed tomography angiography (CCTA) visualizes pericoronary adipose tissue (PCAT) attenuation, which reflects coronary artery inflammation. While PCAT attenuation has been reported to predict future coronary events, phenotypic features of coronary atheroma exhibiting high PCAT attenuation remains to be fully elucidated yet. Objective: To characterize coronary atheroma with a greater vascular inflammation. Methods: We retrospectively analyzed culprit lesions in 69 CAD patients receiving PCI from the REASSURE-NIRS registry (NCT04864171). Culprit lesions were evaluated by both CCTA and near-infrared spectroscopy/intravascular ultrasound (NIRS/IVUS) imaging prior to PCI. PCAT attenuation at proximal RCA (PCAT RCA ) and NIRS/IVUS-derived plaque measures were compared in patients with PCAT RCA attenuation ≥ and &lt; -78.3 HU (median). Results: Culprit lesions with PCAT RCA attenuation ≥ -78.3HU exhibited a greater frequency of maxLCBI 4mm ≥400 (66 vs. 26%, p&lt;0.01), plaque burden ≥70% (94 vs. 74%, p=0.02) and spotty calcification (49 vs. 6%, p&lt;0.01). whereas positive remodeling (63 vs. 41%, p=0.07) did not differ between two groups. On multivariate analysis, maxLCBI 4mm &gt;400 (OR=4.07; 95%CI=1.12-14.74, p=0.03), plaque burden ≥70% (OR=7.87; 95%CI=1.01-61.26, p=0.04), and spotty calcification (OR=14.33; 95%CI=2.37-86.73, p&lt;0.01) independently predicted high PCAT RCA attenuation. Of note, while the presence of only one plaque feature did not necessarily elevate PCAT RCA attenuation (p=0.22), lesions harbouring two or more features were significantly associated with higher PCAT RCA attenuation (Figure). Conclusion: More vulnerable plaque phenotypes were observed in patients with PCAT RCA attenuation. Our findings suggest PCAT RCA attenuation as the presence of profound disease substrate, which potentially benefits from anti-inflammatory agents.
Abstract 11528: Neurotrophic Signaling Pathway Dysregulation, Cardiac Amyloidosis, and Innervation Impairment in the Tg2576 Model of Alzheimer's Disease
Authors: Andrea Elia, Rebecca Parodi-Rullan, Rafael Vazquez-Torres, Silvia Fossati
Journal: Circulation (2022)

Alzheimer's disease (AD) is a complex and incurable neurodegenerative disorder characterized by cerebral amyloid β (Aβ) deposition and tau pathology, accompanied by a gradual loss of the two main neuromodulators, NGF and BDNF. The progressive degeneration of the cerebral neuro-signaling pathways triggers a gradual decline in neurotrophic factors with significant derangement of the peripheral nervous system. This may culminate in detrimental effects on other organs, including the heart. However, whether and how AD modulates neurotrophins, innervation, and amyloidosis in the cardiac tissue is still undefined. Here, we investigated, for the first time, cardiovascular remodeling and neuro signaling pathway dysregulation in a mouse model of Alzheimer’s disease. Hence, 12 months old Tg2576 transgenic mice, a model of cerebral amyloidosis, were compared to age-matched WT littermates. Echocardiographic analysis showed significant deterioration in LV function, evidenced by a severe decline both in ejection fraction and fraction shortening percentage in the Tg2576 group compared to WT mice. Tg2576 mice exhibited a relevant increase in interstitial fibrosis, with progressive accumulation of amyloid aggregates, resulting in severe cardiac nervous system dysfunction. The transgenic line showed a remarkable decrease in cardiac nerve fiber density, both adrenergic (stained with tyrosine hydroxylase- TH) and regenerating nerve endings (labeled with GAP-43) compared to the WT mice. This myocardial denervation was associated with a robust reduction in NGF and BDNF protein expression both at the neuronal and cardiac level, accompanied by a significant decline in GAP-43 activity in the heart and cerebral cortex lysates of Tg2576 mice. Additionally, human neuroblastoma cells (SH-SY5Y) challenged with human Aβ-40 or Aβ-42 oligomers showed a severe downregulation of both BDNF and GAP-43 protein levels. Overall, our evidence highlights a possible detrimental effect of cerebral amyloidosis on the peripheral nervous system and cardiac tissue, providing potential therapeutic targets, such as the neuro-signaling pathway, to prevent or delay some of the effects caused by AD on the cardiovascular system.
Abstract 12045: Mapping the CaV1.2 Interactome in Rat Heart in vivo
Authors: Jared S. Kushner, Aaron Rodriques, Sergey Zakharov, Alexander Katchman, STAVROS FANOURAKIS, Steven Marx
Journal: Circulation (2022)

Introduction: The Ca2+ channel CaV1.2 is an essential part of excitation contraction coupling, neurotransmission and vascular tone. Identifying protein partners of CaV1.2 is critical to make mechanistic insights into these fundamental processes. Prior CaV1.2 proximity proteomes used APEX labeling, which labels other amino acids, introduces oxidative stress and is catalyzed ex vivo. Hypothesis: α1C-TurboID knockin rats can generate tissue specific interactomes in vivo, in cells with intact cell and matrix contacts, which may differ substantially from interactomes made from ex vivo peroxidase catalyzed labeling. Methods: CRISPR/Cas9 homology directed repair (HDR) was applied to rat spermatogonial stem cells with a targeting vector that includes cacna1c exon 44, coding the C-terminus of CaV1.2, and birA*, which codes TurboID, cloned 3’ to the stop codon (Fig A). Figures were made with Biorender. Results: Streptavidin blotting of brain and heart lysates demonstrated robust biotinylation in knockin rats (Fig B). In paced heart myocytes, α1C-TurboID produces Ca2+ transients and responds appropriately to adrenergic stimulation (Fig C), indicating proper localization to the sarcolemma. Expression of α1C-TurboID does not alter systolic function (Fig D). Mass spectrometry of heart lysates affinity purified on streptavidin beads identified 629 proteins, of which 454 were significantly enriched in knockin rats. These include known sarcolemmal proteins and interactors of CaV1.2 (Fig E), which was confirmed by antibody detection (Fig F). 73% of these 454 proteins were not significantly enriched in the APEX-α1C proteome. Conclusion: TurboID fusion to CaV1.2 generates a reliable and substantially different proteome compared to other techniques. Successful in vivo characterization of the channel interactome confirms α1C-TurboID rats will be a powerful tool for identifying changing protein networks across developmental stages, tissues, and disease models.
Abstract 11161: Thymic Hemorrhage – A Cause for Cardiac Arrest?
Authors: Sana Riaz, Paul Thompson
Journal: Circulation (2022)

Introduction: Thymic hemorrhage is a rare cause of sudden cardiac death, particularly in adults. We present a 35- year- old with sudden “cardiac” death secondary to thymic hemorrhage. Case: A 35-year-old healthy man presented following witnessed cardiac arrest. CPR was initiated immediately. The initial rhythm was shockable, he was defibrillated, and ROSC was achieved. He was intubated on site and transferred to the hospital. Initial labs were negative for electrolyte derangements and drugs of abuse. His high-sensitivity troponin T was 238 ng/L (nl&lt;23 ng/L) and subsequently trended downward. His electrocardiogram showed non-specific ST-T abnormalities. His echocardiogram showed an ejection fraction of 25 to 29% with global hypokinesis. He was extubated on day 4 and scheduled for coronary angiography. On day 5, when he attempted to get out of bed, he lost consciousness and became pulseless. His initial rhythm was PEA, but with episodes of ventricular fibrillation during CPR, he was shocked accordingly. He had prolonged CPR, therefore, obviating advanced therapies. His autopsy showed only thymic hemorrhage. His coronary arteries were normal, with no signs of myocardial injury or myocarditis. Conclusion: Massive acute thymic hemorrhage is extremely rare in adults but is a rare but recognized cause of sudden death in utero and infants. There are only two reported cases of thymic hemorrhage in adults in the literature. Both the patients were nearly 40-year-old men who presented with chest pain. Initial imaging was consistent with mediastinal widening requiring thoracotomy that demonstrated hemorrhagic thymus. Similar to our patient, the reported cases were young men with no prior history of trauma. In contrast, our patient presented with cardiac arrest, and initial imaging was negative for mediastinal widening. The underlying etiology of cardiac arrest from thymic hemorrhage is poorly understood. Right atrial compression from acute hemorrhage of a benign thymic tumor was postulated as the cause of sudden death in a previously healthy 15-year-old boy. Our patient is a rare case since there are, to our knowledge, no reported cases in the literature of thymic hemorrhage as the cause of death in adults.